Do you know about the drugs your pet will get? Does your vet use drugs in ways unapproved by the Food and Drug Administration? You may be surprised by the answer.
Veterinarians commonly administer or prescribe drugs “extra-label,” or in ways unapproved by the FDA’s Center for Veterinary Medicine (CVM), to treat a variety of conditions and diseases. The FDA, the government agency responsible for overseeing drug safety, allows the widespread practice because it does not want to interfere with medical decision-making. Indeed, the extra-label use of drugs has saved the lives of many pets, particularly when there are no alternatives for treatment of severe and chronic illnesses.
While vets are allowed to use drugs in ways beyond what’s listed on their FDA approved labels, drug companies and their representatives cannot promote or recommend such use.
New drugs must undergo rigorous clinical trials to prove they’re safe before the FDA will approve them. The agency bans drug manufacturers from promoting or recommending drugs to vets for any use not on their FDA approved labels to keep companies from skirting requirements to test the drugs’ safety and efficiency before they go to market.
So how do veterinarians get extra-label information to use on our pets? One way is through Continuing Medical Education (CME) seminars - oftentimes sponsored and paid for by drug companies.
“In general, the FDA does not intend to interfere with…continuing medical education of veterinary practitioners,” said Linda Grassie, communications director at the FDA. “However,” she added, “continuing medical education events are frequently paid for by drug sponsors.”
And when drug sponsors promote their products in ways unapproved by the FDA, “this tends to violate the Federal Food, Drug, and Cosmetic Act,” said Grassie.
Veterinarians at the Sylvania Veterinary Hospital, on Holland-Sylvania Road, say they learned about the unapproved uses of Domitor (medetomidine), a potent sedative for dogs, at CME seminars sponsored by Pfizer, which manufactures the drug.
The hospital routinely uses Domitor on dogs after surgery, a use unapproved by the FDA.
Domitor, according to its label, can be used in dogs undergoing short procedures, such as teeth cleaning and minor surgeries not requiring muscle relaxation.
Robert Esplin and Ross Mahowald, veterinarians at Sylvania Veterinary Hospital, said using Domitor on dogs after surgery was discussed at seminars funded by the drug giant as part of Pfizer’s DALE (Domitor Antisedan Local Expert) program.
“We had very limited material on Domitor before I went to the seminar,” Mahowald said. "We discussed how Domitor was used, different methods, and how it is used in different species.”
Mahowald was among 400 veterinarians invited by Pfizer to go on two all-expense paid trips to Chicago to attend the seminars, said Esplin, who occasionally appears on Channel 13's "Ask the Expert," segment and "Ask Dr. Bob" on radio station Star 105 FM. Pfizer chooses vets already using the drug at a "high rate" to participate in the DALE program, according to Pfizer. Following the seminars, Mahowald signed a contract with Pfizer to hold seminars for area veterinarians to discuss the “new uses” of Domitor. Pfizer pays Mahowald and other “DALEs” for each seminar they hold.
S. Kristina Wahlstrom, DVM, MS, group director, U.S. Companion Animal Veterinary Operations for Pfizer, said the company does not recommend or promote unapproved uses of Domitor at DALE seminars because it would violate FDA rules and regulations.
She agreed veterinarians in the DALE program sign contracts to be "agents" of the drug company upon completion of the seminars, but “they are under the same regulations we are, in that they cannot promote the extra-label use of Domitor.”
DALEs can tell other vets about Domitor's unapproved uses, but only if they are asked, per FDA regulations, she said.
“If someone asks them about an extra-label use, they have to tell the vet that what they're considering doing with the drug is extra-label,” she said. “The DALE can then give the vet the information, if they have it, on the specific extra-label use. DALEs then have to remind the vet again that it is an extra-label use.”
Robert Fauteux, public relations representative at Pfizer, said DALEs, as agents of Pfizer, are "obligated to comply with the regulations that govern Pfizer employees.”
But Mahowald called such regulations “a matter of semantics.”
“I believe discussion is the same as recommendation,” said Mahowald. “When I signed the contract, I am acting as a representative of Pfizer and I am able to discuss off-label use with other vets.”
Barry Poole, of the FDA, said drug companies, and their representatives, cannot recommend or promote drugs for unapproved uses “either in writing or by word of mouth.”
“You can’t recommend off-label,” he said. “That is promoting. That’s what the law says.”
Pfizer pays for the travel, lodging and meals of veterinarians who attend DALE seminars. Additionally, the company pays vets $500 in honoraria to compensate for their time, said Fauteux.
When drug companies promote or recommend the unapproved uses of drugs, the FDA is concerned about safety, said Grassie.
“We do not have evidence of the safety and effectiveness of the drug for the unapproved indication,” she said. Promoting unapproved uses of drugs “may mislead a medical or veterinary practitioner to use a product inappropriately.”
Clinical trials of Domitor, approved by the FDA in 1996, concluded the sedative is mostly safe and effective so long as it's used "according to the label."
Domitor, according to its label, should not be used in dogs with underlying health conditions, including liver, heart and kidney disease, respiratory disorders, fatigue, dogs that are in shock, or are severely debilitated. Special care is recommended when treating very young animals, debilitated older animals, coughing dogs, or dogs in poor general condition.
Sylvania Veterinary Hospital, which claims to be the only facility in northwest Ohio that offers round the clock care, routinely uses Domitor on dogs after surgery to keep them sedated and quiet – a use unapproved by the FDA and not included on the drug’s label.
Facts on label
Some experts say it’s important for vets to follow the label when using drugs.
The label “is the first source of important facts for veterinarians," Dr. Victoria Hampshire, former adverse drug events coordinator in the office of Surveillance and Compliance in the FDA’s Center for Veterinary Medicine, said in a Jan. 15, 2004 article in the Journal of the American Veterinary Medical Association (JAVMA).
“The label is the result of considerable scientific regulatory review before CVM approves the drug,” said Hampshire, whose investigation of ProHeart6, a long-term heartworm medication for dogs that reportedly caused injury and death to thousands, helped pull it off the market.
“Product precautions, contraindications, safety information, and warnings should identify animal patients that are not good candidates for the medication,” she said.
Pfizer’s Wahlstrom, though, said it should be left up to the discretion of veterinarians to decide how a drug is used.
The drug industry for years has been under fire for illegally promoting unapproved uses of drugs to humans, which reportedly expands their profit margin.
Promotional activities of drug companies and others are substantially motivated by profit and market expansion, William B. Schultz, former deputy commissioner for policy and drug administration in the U.S. Department of Health and Human Services, said before a Senate committee in 1996.
If drug companies were allowed to freely promote the unapproved uses of drugs, “there would be no incentive to conduct or fund the necessary scientific research and to present data to the FDA to verify” their safety and efficacy, said Schultz.
The FDA can take a number of enforcement actions against drug companies and their representatives for promoting or recommending the unapproved uses of drugs, ranging from sending a warning letter, to injunctions, and even criminal prosecution, according to Grassie.
Esplin and Mahowald still support the DALE program and will continue to routinely use Domitor on dogs after surgery. Mahowald's contract with Pfizer has expired, though he said he would not hesitate to hold future seminars on Domitor.
Using Domitor in ways unapproved by the FDA “allows us the flexibility to include the drug in multiple protocols,” Mahowald said.
Esplin agreed. “I have used it enough that I am comfortable and confident to use it in a lot of scenarios.”
The Sylvania Veterinary Hospital promotes Mahowald as a DALE on its website, and touts the “several new ways we will be able to use Domitor” on pets.
“We have used this drug for many years," says the website. Mahowald, described as "a local expert" on the use of Domitor, "will be conducting several seminars for other local veterinarians and their staff."
Since becoming a DALE, Mahowald has yet to hold a seminar, but held a lecture for the Sylvania Veterinary Hospital’s staff concerning the “new uses” of the drug.
Pfizer awarded four veterinarians with trips to Hawaii in May, 2004, to attend a national dermatology conference. A veterinarian at Sylvania Veterinary Hospital was among the winners, according to the facility's website.
Features editor Tammy Wilhelm contributed to this report